Tislelizumab Combined Treatment in Refractory Extranodal NK/T-cell Lymphoma

Sponsor

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (Other)

Overall Status

Recruiting

CT.gov ID

NCT05058755

Collaborator

(none)

Enrollment

Location

Arms

27.4

Anticipated Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Natural killer/T-cell lymphoma (NKTCL) patients with relapsed/refractory disease had very poor outcome. Anti-PD-1 antibody showed promising results in response, but but the complete remission rate of was low. Some anti-PD-1 antibody based regimen showed higher and deeper response in NKTCL patients.

Condition or Disease	Intervention/Treatment	Phase
Natural Killer/T-Cell Lymphoma, Nasal and Nasal-Type	Drug: tislelizumab, azacytidine, lenalidomide Drug: tislelizumab, etoposide, pegaspargase	N/A

Detailed Description

About 20-30% of early-stage patients and 40-60% of late-stage NKTCL patients will experience disease relapse and refractory disease, and the median survival time of relapsed patients is about 6 months. PD-1 antibody is an effective drug for the treatment of patients with relapsed/refractory NKTCL, but the response rate and complete remission rate of monotherapy are low. How to improve the prognosis of patients is an important way to try combination therapy. In this study, we aim to explore the effectiveness and safety of a novel anti-PD-1 antibody, tislelizumab, in combination with different drugs (tislelizumab plus azacytidine and lenalidomide, or tislelizumab plus etoposide and pegaspargase) to treat refractory NK/T.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

62 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of Tislelizumab Combined Treatment in Refractory Natural Killer/T-cell Lymphoma

Actual Study Start Date :

Sep 17, 2021

Anticipated Primary Completion Date :

Dec 30, 2022

Anticipated Study Completion Date :

Dec 30, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: TALE regimen tislelizumab plus azacytidine and lenalidomide	Drug: tislelizumab, azacytidine, lenalidomide tislelizumab, 200mg, iv, day 1, every 21 days. azacytidine, 75mg/m2, ih, days 1-7, every 21 days. lenalidomide, 25mg, po, days 1-14, every 21 days. Other Names: Tileilizhu Dankang
Experimental: TEPA regimen tislelizumab plus etoposide and pegaspargase	Drug: tislelizumab, etoposide, pegaspargase tislelizumab, 200mg, iv, day 1, every 21 days. etoposide, 100mg, iv, days 1-3, every 21 days. pegaspargase, 2000U/m2, day 1, every 21 days Other Names: Tileilizhu Dankang

Arm

Intervention/Treatment

Experimental: TALE regimen

tislelizumab plus azacytidine and lenalidomide

Drug: tislelizumab, azacytidine, lenalidomide

tislelizumab, 200mg, iv, day 1, every 21 days. azacytidine, 75mg/m2, ih, days 1-7, every 21 days. lenalidomide, 25mg, po, days 1-14, every 21 days.

Other Names:

Tileilizhu Dankang

Experimental: TEPA regimen

tislelizumab plus etoposide and pegaspargase

Drug: tislelizumab, etoposide, pegaspargase

tislelizumab, 200mg, iv, day 1, every 21 days. etoposide, 100mg, iv, days 1-3, every 21 days. pegaspargase, 2000U/m2, day 1, every 21 days

Other Names:

Tileilizhu Dankang

Outcome Measures

Primary Outcome Measures

Overall response rate [Week 12 +/-7 days]
The overall response rate will be assessed on Week 12

Secondary Outcome Measures

Complete response rate [Week 12 +/-7 days]
The complete response rate will be assessed on Week 12
Progression free survival [1-year]
Progression free survival is the time from entry onto the treatment until lymphoma progression or death of any reason.
Overall survival [1-year]
Overall survival is defined as the time from entry onto the treatment until death of any reason
Treatment-Related Adverse Events as Assessed by CTCAE v5.0 [Treatment-Related Adverse Events will be assessed and graded by NCI CTCAE v5.0.]
From day 1 of each course of chemotherapy to the 3 months after the last dose of therapy

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with biopsy histopathology, immunohistochemistry and EBER test meet ing the WHO 2016 diagnostic criteria for NK/T cell lymphoma.
With progressive disease after asparaginase-based combined chemotherapy
Have experienced multiple courses of PD-1/PD-L1 treatment with non-responsive or progressive disease.
PET/CT or CT/MRI with at least one measurable lesion or objectively evaluable lesion.
General ECOG score 0-3 points.
The laboratory examination within 1 week before enrollment meets the following conditions:

Blood routine: Hb>80g/L, PLT>50×109/L. Liver function: ALT, AST, TBIL ≤ 2 times the upper limit of normal. Renal function: Cr is normal. Blood coagulation test: plasma fibrinogen ≥1.0g/L. Heart function: LVEF≥50%, ECG did not indicate any acute myocardial infarction, arrhythmia, or atrioventricular block of degree I or more.

Signed informed consent form.
Voluntarily comply with research protocols, follow-up plans, laboratory and auxiliary examinations.

Exclusion Criteria:

Patients with a history of pancreatitis (only patients who are planning to undergo PD1 combined with pegaspargase are excluded).
Severe infections require ICU treatment.
Combined HCV or HIV infection. Patients with HBV infection who receive antiviral treatment at the same time will not be excluded.
There are serious complications such as fulminant DIC.
Impairment of important organ functions: such as respiratory failure, chronic congestive heart failure with NYHA grade ≥2, decompensated liver or kidney insufficiency, hypertension and diabetes that cannot be controlled despite active treatment, nearly 6 years old There were cardio-cerebrovascular thrombotic or hemorrhagic events within months.
Pregnant and lactating women.
Have a history of autoimmune diseases, have disease activity in the past 6 months, and are still receiving oral immunosuppressive therapy within the past three months, and the daily dose of oral prednisone is greater than 10 mg.